Self-renewal and differentiation in squamous cell carcinomas

variety of cell types. It is maintained by stem cell-like tumor propagating cells (TPCs), which self-renew to sustain long-term tumor growth and differentiate into tumor cells with limited proliferative potential. How these cancerous, growth-driving TPCs are specified and how their increased self-renewal and aberrant differentiation programs are established and maintained remains elusive for most human cancers. We recently discovered a squamous cell carcinoma specific PITX1SOX2 and KLF4 dependent, bi-stable transcriptional network, which sheds new light onto the transcriptional circuits that increase self-renewal, inhibit differentiation, and thereby allow for clonal expansion and unlimited cancerous growth in mouse and human squamous cell carcinomas (SCCs) [1]. Skin epithelial cells are the most common site of malignant transformation in humans and they emerged as a paradigm in which tumor initiation, maintenance, and progression can be determined. The malignant transformation of normal skin epithelial stem and progenitor cells (EPCs) into SCC cells involves the acquisition of oncogenic mutations, which hyperactivate the RAS-MAPK pathway, along with additional tumor suppressive mutations and stereotypic transcriptional changes. Once SCCs form, they are mainEditorial